Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range — by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Wei Zheng and colleagues carried out a genome-wide association study of breast cancer in Chinese women and discovered risk variants on 6q25.1 located upstream of the gene encoding estrogen receptor 1 (ESR1). They also found a similar association between the 6q25.1 locus and breast cancer in samples of European ancestry. We carried out a genome-wide association study among Chinese women to identify risk variants for breast cancer. After analyzing 607,728 SNPs in 1,505 cases and 1,522 controls, we selected 29 SNPs for a fast-track replication in an independent set of 1,554 cases and 1,576 controls. We further investigated four replicated loci in a third set of samples comprising 3,472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the gene encoding estrogen receptor α (ESR1), showed strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24–1.49) and 1.59 (1.40–1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend 2.0 × 10−15) in the pooled analysis of samples from all three stages. We also found a similar, albeit weaker, association in an independent study comprising 1,591 cases and 1,466 controls of European ancestry (Ptrend = 0.01). These results strongly implicate 6q25.1 as a susceptibility locus for breast cancer.